Pioglitazone improves endothelium-dependent vasodilation in hypertensive patients with impaired glucose tolerance in part through a decrease in oxidative stress

Background: The aim of this study was to determine pioglitazone treatment restores endothelial function in hypertensive patients with impaired glucose tolerance (IGT). Methods and results: We evaluated the effects of pioglitazone treatment for 12 weeks on forearm blood flow (FBF) responses to acetylcholine and sodium nitroprusside in 34 hypertensive patients with IGT who were randomly divided into a pioglitazone group (n = 17) and an amlodipine monotherapy group (n = 17) and in 34 healthy subjects. Pioglitazone, but not amlodipine, increased the FBF response to acetylcholine and decreased urinary excretion of 8-hydroxy-2'-deoxyguanosine. Pioglitazone did not alter sodium nitroprusside-stimulated vasodilation. N(G)-monomethyl-L-arginine abolished the augmentation of FBF response to acetylcholine after pioglitazone treatment. The increase in maximal FBF response to acetylcholine correlated with the decrease in urinary excretion of 8-hydroxy-2'-deoxyguanosine. Conclusion: Pioglitazone improved endothelial function in hypertensive patients with IGT through an increase in nitric oxide bioavailability by, in part, a decrease in oxidative stress. (C) 2009 Elsevier Ireland Ltd. All rights reserved.